[Science.]Imaging cell lineage with a synthetic digital recording system

Imaging cell lineage with a synthetic digital recording system Science. 2021 Apr 9;372(6538):eabb3099. doi: 10.1126/science.abb3099. Authors Ke-Huan K Chow # 1 , Mark W Budde # 1 , Alejandro A Granados 1 , Maria Cabrera 1 , Shinae Yoon 1 , Soomin Cho 1 , Ting-Hao Huang 1 , Noushin Koulena 1 , Kirsten L Frieda 2 , Long Cai 1 , Carlos Lois 3 , Michael B Elowitz 3 4 Affiliations 1 Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. 2 Spatial Genomics, Inc., Pasadena, CA 91106, USA. 3 Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. melowitz@caltech.edu clois@caltech.edu. 4 Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA. # Contributed equally. PMID: 33833095 DOI: 10.1126/science.abb3099 Abstract During multicellular development, spatial position and lineage history play powerful roles in controlling cell fate decisions. Using a serine integrase-based recording system, we engineered cells to record lineage information in a format that can be read out in situ. The system, termed integrase-editable memory by engineered mutagenesis with optical in situ readout (intMEMOIR), allowed in situ reconstruction of lineage relationships in cultured mouse cells and flies. intMEMOIR uses an array of independent three-state genetic memory elements that can recombine stochastically and irreversibly, allowing up to 59,049 distinct digital states. It reconstructed lineage trees in stem cells and enabled simultaneous analysis of single-cell clonal history, spatial position, and gene expression in Drosophila brain sections. These results establish a foundation for microscopy-readable lineage recording and analysis in diverse systems. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.